Microscopic endometrial perivascular epithelioid cell nodules: a case report with the earliest presentation of a uterine perivascular epithelioid cell tumor
© Fang et al.; licensee BioMed Central Ltd. 2012
Received: 11 August 2012
Accepted: 29 August 2012
Published: 3 September 2012
Perivascular epithelioid cell (PEC) tumors (PEComas) are a family of related mesenchymal tumors composed of PECs which co-express melanocytic and smooth muscle markers. Although their distinctive histologic, immunohistochemical, ultrastructural, and genetic features have been clearly demonstrated, their histogenesis and normal counterpart remain largely unknown. Precursor lesions of PEComas have rarely been reported. We herein describe a tuberous sclerosis patient with microscopic PEC nodules in the endometrium of adenomyosis, pelvic endometriosis, an ovarian endometriotic cyst, and the endometrium of the uterine cavity. The nodules showed a mixture of spindle-shaped and epithelioid cells concentrically arranged around small arteries. The cells exhibited uniform nuclei, light eosinophilic cytoplasm, and immunoreactivity with HMB-45 and CD10. Some nodules revealed continuity with a PEComa in the myometrium. These findings support microscopic endometrial PEC nodules possibly being precursor lesions of uterine PEComas. The wide distribution of the nodules in the pelvis may be related to the multicentricity of PEComas in tuberous sclerosis patients. Owing to the immunoreactivity with CD10, microscopic endometrial PEC nodules may be misinterpreted as endothelial stromal cells unless melanocytic markers are stained. To the best of our knowledge, this is a case with the earliest manifestation of PEC lesions occurring in the endometrium.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9658280017862643
KeywordsPerivascular epithelioid cell PEComa Lymphangioleiomyomatosis CD10 Adenomyosis Endometriosis Tuberous sclerosis
Neoplasms with perivascular epithelioid cell (PEC) differentiation (PEComas), as defined by the World Health Organization, are a family of mesenchymal tumors composed of histologically and immunohistochemically distinctive PECs, characteristically expressing both melanocytic and smooth muscle markers . The concept of “PEC’ was first proposed by Bonetti et al. to identify a novel cell type, which exhibited an epithelioid appearance, clear-eosinophilic cytoplasm, and a perivascular distribution in renal angiomyolipoma (AML), clear-cell sugar tumor (CCST) of the lung, and lymphangioleiomyomatosis (LAM) . Since that time, PEComas have been reported at a wide variety of anatomic sites [3–5]. In the female genital tract, PEComas most frequently affect the uterus . AML, LAM, sclerosing PEComa, and PEComa-not otherwise specified (NOS) were described in the uterus [6–16]. We herein report a unique case of microscopic endometrial PEC nodules, which have never been reported in the literature, and they perhaps represent the earliest manifestation of uterine PEComas. We discuss their histologic and immunohistochemical features, the relationship between the microscopic PEC nodules and PEComas of the female genital tract, and their clinical significance.
A 29-year-old woman had suffered from abnormal vaginal bleeding and severe dysmenorrhea for a long time. Urinary frequency was noted, with exacerbation during menstruation. The patient was known to have tuberous sclerosis which presented with epilepsy and adenoma sebaceum when she was 19 years old. She underwent a left nephrectomy for renal cell carcinoma and a right partial nephrectomy for AML at 20 years old. Ultrasonography showed a poorly demarcated heterogeneous area measuring 4.7 cm in the largest dimension in the myometrium. Debulking surgery for adenomyosis, ablation of the pelvic endometriosis, and cystectomy of the left ovary were performed. Two years later, the patient still complained of dysmenorrhea and diarrhea aggravated during menstruation. She received a second surgery with a clinical diagnosis of endometriosis. The gynecologist found severe fibrous adhesion and endometriosis in the pelvic cavity. A supracervical hysterectomy and bilateral salpingo-oophorectomy were performed. The follow-up information revealed no evidence of recurrent or metastatic disease 168 months after the hysterectomy.
Materials and methods
Antibodies used in this study
Dako, Carpentaria, CA, USA
Smooth muscle actin
Dako, Carpentaria, CA, USA
Dako, Carpentaria, CA, USA
Novocastra, Newcastle Upon Tyne, UK
Novocastra, Newcastle Upon Tyne, UK
Novocastra, Newcastle Upon Tyne, UK
Early or precursor perivascular epithelioid cell lesions reported in the uterus
Sites of early or precursor PEC lesions / size
Histopathology of early or precursor PEC lesions
Associated pathologic findings and important clinical features
Fadare 2004 
(1) Myometrium, small bowel lamina propria, and ovarian hilum.
Aggregates of epithelioid cells with eosinophilic cytoplasm and vacuolated cytoplasm in an occasional perivascular distribution, no cytologic atypia.
Positive for HMB-45, Melan-A, SMA, desmin, and PR.
(1) Cervical PEComa.
(2) < 1 mm.
(2) Associated with tuberous sclerosis.
(3) No recurrence or metastasis at 35 months’ follow-up.
Liang 2008 
(1) Myometrium, cervical wall, and ovarian hilum.
Bland-looking epithelioid clear cells
(1) Positive for HMB-45, Melan-A, SMA, and myogenin.
(1) Uterine malignant PEComa and LAM of pelvic lymph nodes.
(2) 1-5 mm.
(2) Negative for desmin, ER, and PR.
(2) Associated with tuberous sclerosis;
(3) No follow-up data.
Clay 2010 
Epithelioid cells in close approximation with lymphatic-type vessels, clear to granular and eosinophilic cytoplasm.
(1) Positive for HMB-45, Mart-1, SMA, and desmin.
(1) Early LAM
(2) <2 mm.
(2) Negative for CD10.
(2) No tuberous sclerosis.
(3) No follow-up data.
The present case
(1) Endometrium of adenomyosis, pelvic endometriosis, ovarian endometriotic cyst, and the endometrium of the uterine cavity.
Aggregates of spindle-shaped and epithelioid cells in a perivascular distribution, light eosinophilic cytoplasm, no cytologic atypia
(1) Positive for HMB-45, SMA, CD10 and PR.
(1) Uterine PEComa, sclerosing PEComa, and LAM.
(2) < 1 mm.
(2) Negative for desmin and ER
(2) Associated with tuberous sclerosis
(3) No recurrence or metastasis at 168 months’ follow-up
AMLs, the most common member of PEComas, were reported to have similar early PEC lesions, which were designated as microharmatomas, small mesenchymal nodules, or intraglomerular lesions [4, 23–25]. Such lesions were confined within glomeruli or located outside glomeruli. They contained only epithelioid cells or a mixture of epithelioid cells and adipocytes. Immunoreactivity with HMB-45 was consistently noted in epithelioid cells. Chowdhury et al., analyzing the histologic relationship between small mesenchymal nodules and AML, found that small-sized mesenchymal nodules tended to only be comprised of epithelioid cells without adipocytes or blood vessels, compared to large-sized ones which contained epithelioid cells, adipocytes, and blood vessels . These findings support small mesenchymal nodules being the buds of AMLs. Precursor PEC lesions were also described in association with a urachal PEComa . The precursor lesion, remote from the main urachal PEComa, was composed of capillaries lined by HMB-45-positive clear cells. A gradual transition from the precursor lesions to invasive PEComa nests was observed.
The present case is unique for the early PEC lesions being present in the endometrium, in contrast to other early PEC lesions, which were reported in the myometrium [11, 12, 22] (Table 2). The endometrial distribution of early PEC lesions may account for rare uterine PEComas, which present as polypoid endometrial lesions with minimal myometrial involvement [9, 10]. This also strengthens the supposition that uterine PEComas are distinctive from uterine smooth muscle tumors. Uterine PEComas being a distinct clinicopathologic entity can be challenged by frequent HMB-45 expression in epithelioid and conventional leiomyosarcomas of the uterus [27–29]. The question arises as to whether uterine PEComas are a distinctive entity or whether they represent a subgroup of HMB-45-positive smooth muscle tumors . Since smooth muscle tumors typically originate in the myometrium, the endometrial origin of early PEC lesions supports uterine PEComas being a distinctive tumor. The immunophenotype of early PEC lesions, with diffuse HMB-45 and rare SMA expressions, also argues against their origin from smooth muscle cells.
Another immunophenotypic feature requiring further discussion is CD10 expression. In the present case, CD10 expression was restricted to microscopic endometrial PEC nodules, whereas the well-formed PEComa, LAM, and sclerosing PEComa in the myometrium showed negative CD10 reactivity. CD10 expression was reported in 25 % of uterine PEComas which underwent CD10 staining . Although CD10 reactivity is not low in uterine PEComas, the significance of CD10 expression remains to be elucidated. Herein, we try to clarify the role of CD10. First, CD10 is commonly used to distinguish endometrial stromal nodules/sarcomas from uterine smooth muscle tumors . CD10, although occasionally positive in smooth muscle tumors, is relatively specific for endometrial stromal cells. It would be interesting to determine whether or not the development of uterine PEComas is related to endometrial stromal cells. In CD10-positive uterine PEComas, tumor locations were not limited to the endometrium [10, 32, 33]. CD10 expression was not always detected in uterine PEComas which extensively involved the endometrium . On the basis of the aforementioned findings, the hypothesis that uterine PEComas are derived from endometrial stromal cells is not supported. Second, CD10 is used as a cell surface marker of mesenchymal stem cells and tumor stem cells . It is of paramount importance to understand whether CD10 is a surface marker of tumor stem cells of uterine PEComas. Unfortunately, CD10 is not routinely used in diagnosing PEComas. CD10 staining was not done in the other uterine PEComas with early or precursor PEC lesions [11, 12]. More cases with early or precursor PEC lesions stained with CD10 are required to answer this question.
Moreover, since uterine PEComas may present as endometrial lesions with CD10 expression, PECs may be misinterpreted as endometrial stromal cells, particularly in an endometrial curettage specimen. Plump cells with more abundant clear to light eosinophilic cytoplasm and a radial arrangement around vessels should raise suspicion of the existence of PECs. A misdiagnosis can be avoided by awareness of the existence of endometrial PEComas and assistance with immunostaining using melanocytic markers.
The present case showed microscopic endometrial PEC nodules widely distributed in the endometrium of adenomyosis, pelvic endometriosis, an ovarian endometriotic cyst, and the endometrium of the uterine cavity in a tuberous sclerosis patient. The microscopic endometrial PEC nodules were clearly demonstrated to have progressed into a uterine PEComa. Further studies focusing on early HMB-45-positive PEC nodules may be helpful in clarifying the pathogenesis of PEComas. The role of CD10 in PEComas also needs to be further evaluated.
Written informed consent was obtained from the patient for publication of this Case Report and all accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Clear-cell sugar tumor
Perivascular epithelioid cell
Perivascular epithelioid cell tumor.
- Folpe AL: Neoplasms with perivascular epithelioid cell differentiation (PEComas). World Health Organization Classification of Tumors. Pathology and genetics of tumors of soft tissue and bone. Edited by: Fletcher CDM, Unni KK, Mertens F. 2002, Lyon: ARC Press, 221-222.Google Scholar
- Bonetti F, Pea M, Martignoni G, Zamboni G: PEC and sugar. Am J Surg Pathol. 1992, 16: 307-308. 10.1097/00000478-199203000-00013.View ArticlePubMedGoogle Scholar
- Hornick JL, Fletcher CD: PEComa: what do we know so far ?. Histopathology. 2006, 48: 75-82. 10.1111/j.1365-2559.2005.02316.x.View ArticlePubMedGoogle Scholar
- Martignoni G, Pea M, Reghellin D, Zamboni G, Bonetti F: PEComas: the past, the present and the future. Virchows Arch. 2008, 452: 119-132. 10.1007/s00428-007-0509-1.PubMed CentralView ArticlePubMedGoogle Scholar
- Folpe AL, Kwiatkowski DJ: Perivascular epithelioid cell neoplasms: pathology and pathogenesis. Hum Pathol. 2010, 41: 1-15. 10.1016/j.humpath.2009.05.011.View ArticlePubMedGoogle Scholar
- Fadare O: Perivascular epithelioid cell tumor (PEComa) of the uterus: an outcome-based clinicopathologic analysis of 41 reported cases. Adv Anat Pathol. 2008, 15: 63-75. 10.1097/PAP.0b013e31816613b0.View ArticlePubMedGoogle Scholar
- Sieinski W: Lipomatous neometaplasia of the uterus. Report of 11 cases with discussion of histogenesis and pathogenesis. Int J Gynecol Pathol. 1989, 8: 357-363. 10.1097/00004347-198912000-00007.View ArticlePubMedGoogle Scholar
- Gyure KA, Hart WR, Kennedy AW: Lymphangiomyomatosis of the uterus associated with tuberous sclerosis and malignant neoplasia of the female genital tract: a report of two cases. Int J Gynecol Pathol. 1995, 14: 344-351. 10.1097/00004347-199510000-00010.View ArticlePubMedGoogle Scholar
- Pea M, Martignoni G, Zamboni G, Bonetti F: Perivascular epithelioid cell. Am J Surg Pathol. 1996, 20: 1149-1153. 10.1097/00000478-199609000-00012.View ArticlePubMedGoogle Scholar
- Vang R, Kempson RL: Perivascular epithelioid cell tumor (‘PEComa’) of the uterus: a subset of HMB-45-positive epithelioid mesenchymal neoplasms with an uncertain relationship to pure smooth muscle tumors. Am J Surg Pathol. 2002, 26: 1-13. 10.1097/00000478-200201000-00001.View ArticlePubMedGoogle Scholar
- Fadare O, Parkash V, Yilmaz Y, Mariappan MR, Ma L, Hileeto D, Qumsiyeh MB, Hui P: Perivascular epithelioid cell tumor (PEComa) of the uterine cervix associated with intraabdominal ‘PEComatosis’: A clinicopathological study with comparative genomic hybridization analysis. World J Surg Oncol. 2004, 2: 35-10.1186/1477-7819-2-35.PubMed CentralView ArticlePubMedGoogle Scholar
- Liang SX, Pearl M, Liu J, Hwang S, Tornos C: "Malignant" uterine perivascular epithelioid cell tumor, pelvic lymph node lymphangioleiomyomatosis, and gynecological pecomatosis in a patient with tuberous sclerosis: a case report and review of the literature. Int J Gynecol Pathol. 2008, 27: 86-90. 10.1097/pgp.0b013e318150df37.View ArticlePubMedGoogle Scholar
- Froio E, Piana S, Cavazza A, Valli R, Abrate M, Gardini G: Multifocal PEComa (PEComatosis) of the female genital tract associated with endometriosis, diffuse adenomyosis, and endometrial atypical hyperplasia. Int J Surg Pathol. 2008, 16: 443-446. 10.1177/1066896908316067.View ArticlePubMedGoogle Scholar
- Hornick JL, Fletcher CD: Sclerosing PEComa: clinicopathologic analysis of a distinctive variant with a predilection for the retroperitoneum. Am J Surg Pathol. 2008, 32: 493-501. 10.1097/PAS.0b013e318161dc34.View ArticlePubMedGoogle Scholar
- Lim GS, Oliva E: The morphologic spectrum of uterine PEC-cell associated tumors in a patient with tuberous sclerosis. Int J Gynecol Pathol. 2011, 30: 121-128.View ArticlePubMedGoogle Scholar
- Yang W, Li G, Wei-qiang Z: Multifocal PEComa (PEComatosis) of the female genital tract and pelvis: a case report and review of the literature. Diag Pathol. 2012, 7: 23-10.1186/1746-1596-7-23.View ArticleGoogle Scholar
- Pea M, Bonetti F, Zamboni G, Martignoni G, Riva M, Colombari R, Mombello A, Bonzanini M, Scarpa A, Ghimenton C, Fiore-Donati L: Melanocyte-marker-HMB-45 is regularly expressed in angiomyolipoma of the kidney. Pathology. 1991, 23: 185-188. 10.3109/00313029109063563.View ArticlePubMedGoogle Scholar
- Pea M, Bonetti F, Zamboni G, Martignoni G, Fiore-Donati L, Doglioni C: Clear cell tumor and angiomyolipoma. Am J Surg Pathol. 1991, 15: 199-202. 10.1097/00000478-199102000-00020.View ArticlePubMedGoogle Scholar
- Bonetti F, Pea M, Martignoni G, Zamboni G, Iuzzolino P: Cellular heterogeneity in lymphangiomyomatosis of the lung. Hum Pathol. 1991, 22: 727-728. 10.1016/0046-8177(91)90298-4.View ArticlePubMedGoogle Scholar
- Folpe AL, Goodman ZD, Ishak KG, Paulino AF, Taboada EM, Meehan SA, Weiss SW: Clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres. Am J Surg Pathol. 2000, 24: 1239-1246. 10.1097/00000478-200009000-00007.View ArticlePubMedGoogle Scholar
- Hendrickson MR, Tavassoli FA, Kempson RL, McCluggage WG, Haller U, Kubik-Huch RA: Perivascular epithelioid cell tumor. World Health Organization Classification of Tumors. Pathology and genetics of tumors of the breast and female genital organs. Edited by: Tavassoli FA, Devilee P. 2003, Lyon: IARC Press, 243-Google Scholar
- Clay MR, Gibson P, Lowell J, Cooper K: Microscopic uterine lymphangioleiomyomatosis perivascular epithelioid cell neoplasm: a case report with the earliest manifestation of this enigmatic neoplasm. Int J Gynecol Pathol. 2011, 30: 71-75. 10.1097/PGP.0b013e3181efe08d.View ArticlePubMedGoogle Scholar
- Nagashima Y, Ohaki Y, Tanaka Y, Misugi K, Horiuchi M: A case of renal angiomyolipomas associated with multiple and various hamartomatous microlesions [abtract]. Virchows Arch A Pathol Anat Histopathol. 1988, 413: 177-182. 10.1007/BF00749680.View ArticlePubMedGoogle Scholar
- Chowdhury PR, Tsuda N, Anami M, Hayashi T, Iseki M, Kishikawa M, Matsuya F, Kanetake H, Saito Y: A histopathologic and immunohistochemical study of small nodules of renal angiomyolipoma: a comparison of small nodules with angiomyolipoma. Mod Pathol. 1996, 9: 1081-1088.PubMedGoogle Scholar
- Kiliçaslan I, Güllüoglu MG, Dogan O, Uysal V: Intraglomerular microlesions in renal angiomyolipoma. Hum Pathol. 2000, 31: 1325-1328. 10.1053/hupa.2000.16533.View ArticlePubMedGoogle Scholar
- Weinreb I, Howarth D, Latta E, Ghazarian D, Chetty R: Perivascular epithelioid cell neoplasms (PEComas): four malignant cases expanding the histopathological spectrum and a description of a unique finding. Virchows Arch. 2007, 450: 463-470. 10.1007/s00428-007-0378-7.View ArticlePubMedGoogle Scholar
- Silva EG, Deavers MT, Bodurka DC, Malpica A: Uterine epithelioid leiomyosarcoma with clear cells. Reactivity with HMB-45 and the concept of PEComa. Am J Surg Pathol. 2004, 28: 244-249. 10.1097/00000478-200402000-00013.View ArticlePubMedGoogle Scholar
- Silva EG, Bodurka DC, Scouros MA, Ayala A: A uterine leiomyosarcoma that became positive for HMB45 in the metastasis. Ann Diagn Pathol. 2005, 9: 43-45. 10.1053/j.anndiagpath.2004.10.011.View ArticlePubMedGoogle Scholar
- Simpson KW, Albores-Saavedra J: HMB-45 reactivity in conventional uterine leiomyosarcomas. Am J Surg Pathol. 2007, 31: 95-98. 10.1097/01.pas.0000213346.57391.70.View ArticlePubMedGoogle Scholar
- Fadare O: Uterine PEComa: appraisal of a controversial and increasingly reported mesenchymal neoplasm. Int Semin Surg Oncol. 2008, 5: 7-10.1186/1477-7800-5-7.PubMed CentralView ArticlePubMedGoogle Scholar
- Chu PG, Arber DA, Weiss LM, Chang KL: Utility of CD10 in distinguishing between endometrial stromal sarcoma and uterine smooth muscle tumors: an immunohistochemical comparision of 34 cases. Mod Pathol. 2001, 14: 465-471. 10.1038/modpathol.3880335.View ArticlePubMedGoogle Scholar
- Greene LA, Mount SL, Schned AR, Cooper K: Recurrent perivascular epithelioid cell tumor of the uterus (PEComa): an immunohistochemical study and review of the literature. Gynecol Oncol. 2003, 90: 677-681. 10.1016/S0090-8258(03)00325-1.View ArticlePubMedGoogle Scholar
- Dimmler A, Seitz G, Hohenberger W, Kirchner T, Faller G: Late pulmonary metastasis in uterine PEComa. J Clin Pathol. 2003, 56: 627-628. 10.1136/jcp.56.8.627.PubMed CentralView ArticlePubMedGoogle Scholar
- Maguer-Satta V, Besançon R, Bachelard-Cascales E: Concise review: neutral endopeptidase (CD10): a multifaceted environment actor in stem cells, physiological mechanisms, and cancer. Stem Cells. 2011, 29: 389-396. 10.1002/stem.592.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.